Bottom Line:
Enumeration and molecular characterization of circulating tumor cells isolated from peripheral blood of patients with cancer can aid selection of targeted therapy for patients, monitoring of response to therapies and optimization of drug development, while also providing valuable information about intratumoral heterogeneity.

ABSTRACTEnumeration and molecular characterization of circulating tumor cells isolated from peripheral blood of patients with cancer can aid selection of targeted therapy for patients, monitoring of response to therapies and optimization of drug development, while also providing valuable information about intratumoral heterogeneity.

Fig1: Visualization of circulating tumor cells (CTCs) after isolation with the CellSearch semiautomated system (Janssen Diagnostics). (a) Two CTCs from a blood sample from a cancer patient. Both cells have an oval morphology and have a diameter >4 μm. The nucleus is visible with DAPI (DAP) and they are positively stained for epithelial markers (cytokeratins, CK) but not for CD45 (a leukocyte marker). (b) Two ‘events’ identified as CTCs by the automated system but that were discarded by the trained human operator as each does not fulfill the characteristics of a CTC. APC, allophycocyanin; PE, phycoerythrin.

Mentions:
Methods to capture CTCs from blood rest on their differential physical or immunologic characteristics. The basis for affinity-binding systems used for CTC ‘enrichment’ is the selection of cells expressing certain antigens, such as epithelial cell-adhesion molecules (EpCAMs), and the discard of those cells expressing antigens that are known to be absent on epithelial cells but expressed by other blood cells, such as leukocyte-expressed CD45. Alternatively, CTCs can be isolated based on their distinct physical (size or deformability) or electromagnetic properties [9-11]. The enriched CTC population is then evaluated using an imaging system and, although counting can be completely automated, this step usually requires a certain degree of input from a human operator (Figure 1).Figure 1

Fig1: Visualization of circulating tumor cells (CTCs) after isolation with the CellSearch semiautomated system (Janssen Diagnostics). (a) Two CTCs from a blood sample from a cancer patient. Both cells have an oval morphology and have a diameter >4 μm. The nucleus is visible with DAPI (DAP) and they are positively stained for epithelial markers (cytokeratins, CK) but not for CD45 (a leukocyte marker). (b) Two ‘events’ identified as CTCs by the automated system but that were discarded by the trained human operator as each does not fulfill the characteristics of a CTC. APC, allophycocyanin; PE, phycoerythrin.

Mentions:
Methods to capture CTCs from blood rest on their differential physical or immunologic characteristics. The basis for affinity-binding systems used for CTC ‘enrichment’ is the selection of cells expressing certain antigens, such as epithelial cell-adhesion molecules (EpCAMs), and the discard of those cells expressing antigens that are known to be absent on epithelial cells but expressed by other blood cells, such as leukocyte-expressed CD45. Alternatively, CTCs can be isolated based on their distinct physical (size or deformability) or electromagnetic properties [9-11]. The enriched CTC population is then evaluated using an imaging system and, although counting can be completely automated, this step usually requires a certain degree of input from a human operator (Figure 1).Figure 1

Bottom Line:
Enumeration and molecular characterization of circulating tumor cells isolated from peripheral blood of patients with cancer can aid selection of targeted therapy for patients, monitoring of response to therapies and optimization of drug development, while also providing valuable information about intratumoral heterogeneity.

ABSTRACTEnumeration and molecular characterization of circulating tumor cells isolated from peripheral blood of patients with cancer can aid selection of targeted therapy for patients, monitoring of response to therapies and optimization of drug development, while also providing valuable information about intratumoral heterogeneity.